A noninvasive technique for measuring local cerebral blood flow (LCBF) by xenon-enhanced x-ray transmission computed tomography (Xe/Ct) has been developed and a broad range of clinical applications reported. The Xe/Ct CBF method has been integrated into current CT technology and it has the potential to become widely available at a relatively low cost compared to other tomographic CBF techniques. Xe/Ct CBF also provides direct anatomic reference of CBF information to the baseline CT, relatively high resolution, and the unique ability to record low flow values that predict the nonviability of tissue. Although preliminary reports suggest that Xe/Ct CBF information could be of clinical utility in the early diagnosis and management of emergent clinical problems, especially stroke or head trauma, the observation that the inhalation of xenon can elevate CBF precludes its use in these areas. The concern has been expressed that a xenon-induced rise of CBF could elevate the intracranial pressure in a patient with a mass lesion or cause a reduction of needed blood flow in an ischemic area. An unpredictable elevation of CBF due to xenon would also disqualify it as a useful tracer of CBF. A series of studies is proposed to systematically examine the extent and time course of CBF activation that accompanies xenon inhalation. Dynamic flow changes, as well as global and local flow alterations, will be examined, as will the intracranial pressure, electroencephalogram, and the metabolic rates of oxygen and glucose. The interaction of the changes in these physiological measurements to variations in the pCO2 and/or the pO2 will also be detafled, as will the dose response to a range of xenon concentrations. Models of an intracranial mass lesion and a focal ischemic injury will be created, and the physiological effect of xenon inhalation examined. Until the proposed questions are fully answered, the potential application of Xe/CT CBF in clinical medicine will remain limited.